Neuroblastomas (NB) and Ewing's Sarcoma/peripheral Primitive Neuro-ectodermal Tumors (ES/PNET) are pediatric cancers of neural crest orgin. It has been suggested that the control of the differentiation program o f the sympathetic lineage of NBs versus the parasympathetic lineage of ES/PNETs proceed in a linear fashion. Somatic cell hybridization of NB cell lines and ES/PNET cell lines show that NB-specific markers are repressed, and the transfection of NB with the Ews/FLI-1 chimeric gene characteriztically found in ES/PNETs show similar results. This project will characterize the Ews/FLI-1's role in cell cycle control utilizing western blot analysis to monitor expression of p53 and pRb, immunofluorescence to monitor p53 localization and protein half life experiments to monitor p53 stability. This project will also utilize microchip array techinology to study the mechanism and pathway of the Ews/FLI-1 oncogene.